Oral cavity squamous cell carcinoma (OCSCC) has a recognized propensity for cervical lymphatic dissemination, and the presence and extent of nodal disease are important factors influencing recurrence and survival. Even when cervical lymph nodes appear negative on clinical examination and radiological assessment (cN0/rN0), microscopic metastatic disease may remain undetected. This creates an important challenge in determining the appropriate management of the clinically negative neck. Among the primary tumor characteristics, depth of invasion (DOI) has been consistently linked to the likelihood of cervical nodal involvement and patient prognosis and is now incorporated into contemporary staging systems for oral cavity cancer [1-3]. Elective neck dissection (END) serves two important purposes in patients with a clinically negative neck: treatment of potential occult regional disease and provision of definitive pathological staging. Evidence from randomized clinical trials and pooled analyses has demonstrated improved oncological outcomes with elective compared with therapeutic neck dissection in appropriately selected patients with node-negative oral cavity cancer [4,5]. Beyond the decision to perform END, the number of lymph nodes retrieved and examined may influence the quality of pathological staging and potentially provide prognostic information. Previous studies have suggested that a greater lymph node yield (LNY), with particular attention to a threshold of 18 nodes, may be associated with improved survival following neck dissection [6]. The lymph node ratio (LNR) has subsequently emerged as another method of characterizing nodal disease. LNR represents the proportion of examined lymph nodes that contain metastatic disease and therefore incorporates both the extent of nodal metastasis and the total number of nodes assessed pathologically. Several studies have reported an association between increasing LNR and adverse survival outcomes in OCSCC [7]. The detection of occult nodal metastases remains particularly relevant in patients considered cN0, while pathological features such as extranodal extension (ENE) may further refine assessment of regional disease burden and prognosis [8]. In addition, contemporary evidence evaluating sentinel lymph node-based approaches to the clinically negative neck highlights the importance of accurate pathological assessment when selecting patients for appropriate treatment and subsequent risk stratification [9]. Although both LNY and LNR have been investigated as prognostic markers, their relative clinical significance remains uncertain, particularly among patients with cN0/rN0 OCSCC undergoing END. The commonly used threshold of 18 lymph nodes has not demonstrated uniform prognostic performance across different patient populations and treatment settings, while more recent evidence has emphasized the potential value of LNR as a measure of nodal disease burden [10]. Furthermore, evidence from South Asian populations remains relatively limited, and it is uncertain whether thresholds derived from other populations can be directly applied to this setting. The present study was therefore undertaken to investigate the prognostic relevance of LNY and LNR in patients with cN0/rN0 OCSCC treated with END. We evaluated the frequency of occult pathological nodal metastases, pathological nodal characteristics, recurrence patterns, overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS), and examined survival outcomes according to predefined LNY and LNR categories.

Study Design and Patient Selection This retrospective cohort study included consecutive adult patients with histologically confirmed oral cavity squamous cell carcinoma (OCSCC) who were treated at the Pakistan Institute of Medical Sciences, Islamabad, from January 2022 through January 2026. Patients were eligible if they had clinically and radiologically node-negative disease (cN0/rN0) and underwent curative-intent resection of the primary tumor combined with elective neck dissection (END). Patients were excluded if they had recurrent disease, a history of previous neck dissection or head and neck radiotherapy, clinically or radiologically evident cervical nodal disease, distant metastases, non-squamous histology, palliative treatment, or incomplete pathological or follow-up information. The study was conducted and reported in accordance with the STROBE recommendations [11]. Clinical, Surgical, and Pathological Assessment Preoperative assessment of the cervical lymph nodes consisted of clinical examination together with contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI). Relevant demographic, clinical, operative, pathological, treatment, and follow-up information was retrieved from institutional medical records. The collected variables included age, sex, primary tumor subsite, pathological T stage, depth of invasion (DOI), histological grade, perineural invasion (PNI), lymphovascular invasion (LVI), surgical margin status, extranodal extension (ENE), extent of neck dissection, and adjuvant treatment. Tumor staging was performed according to the American Joint Committee on Cancer (AJCC) TNM classification applicable during the study period [12]. Lymph Node Variables and Outcomes Lymph node yield (LNY) was defined as the total number of lymph nodes retrieved from the neck dissection specimen and subsequently examined histopathologically. Lymph node ratio (LNR) was calculated by dividing the number of metastatic lymph nodes by the total number of lymph nodes examined and expressing the resulting value as a percentage. LNY and LNR were considered as continuous variables in the analysis, with LNY additionally categorized into <18 and ≥18 nodes and LNR categorized into <19% and ≥19%. Previous studies have demonstrated an association between higher LNR and poorer outcomes in OCSCC, although the thresholds used to define prognostically relevant LNR categories have varied between studies [6,7]. The primary outcome was overall survival (OS), defined as the time from the date of surgery to death from any cause. Secondary outcomes included disease-free survival (DFS), disease-specific survival (DSS), and locoregional recurrence. Follow-up duration was measured from the date of surgery until the last documented clinical follow-up or death. Statistical Analysis Statistical analyses were performed using IBM SPSS Statistics for Windows, version 27.0 (IBM Corp., Armonk, NY, USA). Continuous variables were summarized using mean ± standard deviation or median with interquartile range (IQR), depending on the distribution of the data, whereas categorical variables were presented as frequencies and percentages. Comparisons between categorical variables were performed using the chi-square test or Fisher's exact test, as appropriate. Overall survival was estimated using the Kaplan-Meier method, and survival distributions were compared using the log-rank test. Statistical significance was defined as a two-sided p value <0.05. Ethical Considerations The study received approval from the Head of the Department of ENT–Head and Neck Surgery, Pakistan Institute of Medical Sciences, Islamabad (approval number: F02/03/2021/57489ENT). Given the retrospective nature of the study, the requirement for individual informed consent was waived. All patient information was handled confidentially throughout the study.

Patient and Tumor Characteristics A total of 250 patients were included in the final analysis (Figure 1). The mean age was 53.9± 11.3 years, and 156 (62.4%) patients were male. The most common tumor subsite was buccal mucosa (83, 33.2%). T1–T2 tumors accounted for 57 (22.8%) cases, while 192 (77.2%) had T3–T4 disease. The median DOI was 16.7 mm. Baseline characteristics are shown in Table 1. Characteristic Number (N=250) Percentage (%) Age, years Mean age 53.9± 11.3 — Sex Male 156 62.4 Female 94 37.6 Primary tumor site Oral tongue 74 29.6 Floor of mouth 17 6.8 Buccal mucosa 83 33.2 Gingiva/alveolus 59 23.6 Retromolar trigone 11 4.4 Other 6 2.4 Pathological T stage T1 17 6.8 T2 40 16.0 T3 90 36.0 T4 103 41.2 Depth of invasion (DOI) Median DOI, mm 16.7 — Histological grade Well differentiated 77 30.8 Moderately differentiated 134 53.6 Poorly differentiated 39 15.6 Abbreviations: DOI, depth of invasion. Nodal Characteristics The median lymph node yield (LNY) was 20 nodes; 104 (41.6%) patients had an LNY <18, while 146 (58.4%) had an LNY ≥18. Occult pathological nodal metastases were identified in 78 (31.2%) patients. Extranodal extension (ENE) was present in 26 (10.4%) patients, and the median lymph node ratio (LNR) was 16%. Surgical and pathological nodal characteristics are presented in Table 2. Table 2. Surgical and Pathological Nodal Characteristics Surgical and Pathological Nodal Characteristics Number (n) Percentage (%) Median lymph node yield (LNY) 20 — LNY <18 104 41.6 LNY ≥18 146 58.4 Occult pathological nodal metastases 78 31.2 Extranodal extension (ENE) 26 10.4 Median lymph node ratio (LNR) 16% — Abbreviations: ENE, extranodal extension; LNR, lymph node ratio; LNY, lymph node yield. Oncological Outcomes During a mean follow-up of 28.4 ± 8.9 months, 67 (26.8%) patients developed recurrence and 27 (10.8%) died. Local, regional, and distant recurrence occurred in 45 (18.0%), 39 (15.6%), and 15 (6.0%) patients, respectively; patients with multiple sites of recurrence were included in more than one category. The 5-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were 70.01%, 66.32%, and 80.65%, respectively. Oncological outcomes are summarized in Table 3. Table 3. Oncological Outcomes Oncological Outcome Number (n) Percentage (%) Recurrence 67 26.8 Death 27 10.8 Local recurrence 45 18.0 Regional recurrence 39 15.6 Distant recurrence 15 6.0 5-year overall survival (OS) — 70.01 5-year disease-free survival (DFS) — 66.32 5-year disease-specific survival (DSS) — 80.65 Abbreviations: DFS, disease-free survival; DSS, disease-specific survival; OS, overall survival. Survival and Prognostic Analysis Kaplan-Meier analysis showed that patients with LNY ≥18 nodes had a numerically higher 5-year OS than those with LNY <18 nodes (72.73% vs. 67.41%); however, this difference was not statistically significant (log-rank p=0.234). In contrast, 5-year OS differed significantly between the LNR groups (89.92% vs. 55.67%, log-rank p=0.004), indicating a significant association between LNR category and OS in this cohort (Table 4). Table 4. Kaplan-Meier Analysis of Overall Survival According to LNY and LNR Variable Group 5-year OS (%) P- value Lymph node yield (LNY) <18 nodes 67.41 0.234 ≥18 nodes 72.73 Lymph node ratio (LNR) < 19% 89.92 0.004 ≥19% 55.67 Abbreviations: LNR, lymph node ratio; LNY, lymph node yield.

This study examined the prognostic relevance of elective neck dissection (END), lymph node yield (LNY), and lymph node ratio (LNR) in patients with clinically and radiologically node-negative (cN0/rN0) oral cavity squamous cell carcinoma (OCSCC). Among 250 patients, occult pathological nodal metastases were detected in 31.2%, highlighting that cervical metastases may remain undetected despite negative clinical and radiological assessment. This observation is consistent with previous reports describing a substantial rate of occult nodal disease in cN0 oral cavity cancer [8,13]. The presence of occult nodal disease supports the role of END in appropriately selected patients. Randomized evidence has demonstrated improved disease-free and overall survival with elective rather than therapeutic neck dissection in clinically node-negative oral cancer [4]. Although our study did not include an observation group, the detection of occult metastases in nearly one-third of patients emphasizes the staging value of pathological neck assessment. The median LNY in our cohort was 20 nodes, and 58.4% of patients had a yield of at least 18 nodes. An 18-node threshold has previously been proposed as a measure of adequate nodal evaluation and has been associated with improved survival in OCSCC [6]. In our cohort, however, this threshold was not significantly associated with OS. Five-year OS was 72.73% in patients with LNY ≥18 compared with 67.41% in those with LNY <18 (log-rank p=0.234). Thus, although the ≥18-node group showed numerically higher survival, the difference did not reach statistical significance. These findings differ from earlier work supporting the 18-node threshold. Ebrahimi et al. reported poorer survival with lower nodal yields and proposed 18 nodes as a minimum standard for adequate nodal assessment [6]. More recent evidence, however, suggests that the prognostic value of a fixed LNY threshold may vary according to patient characteristics, surgical technique, pathological processing, tumor stage, and treatment [10]. Therefore, LNY alone may not fully reflect the biological burden of nodal disease. In contrast, LNR showed a significant association with OS in our cohort. Five-year OS was 89.92% among patients with lower LNR compared with 55.67% among those with higher LNR (log-rank p=0.004). LNR incorporates both metastatic nodal burden and the total number of examined nodes and may therefore provide a measure of nodal disease burden that is less dependent on absolute nodal counts [7]. Ebrahimi et al. previously reported that increasing LNR was associated with regional failure and poorer disease-specific and overall survival in OSCC [7]. Similar findings have been reported by other investigators. Spoerl et al. demonstrated an independent association between LNR and overall and recurrence-free survival in a multicenter population-based cohort [13]. However, their reported cutoff of 5.5% was considerably lower than the 19% threshold used in our study. This variation across studies indicates that there is no universally accepted LNR cutoff and that reported thresholds may depend on patient population and methodology. The prognostic relevance of LNR has also been supported by other studies evaluating nodal characteristics in OCSCC [10,14]. A study of floor-of-mouth squamous cell carcinoma reported a threshold close to 17.5%, which is relatively similar to the 19% cutoff used in our cohort [15]. Nevertheless, our 19% threshold should be regarded as a study-specific categorization rather than a universally applicable prognostic boundary. The stronger survival separation observed with LNR may be explained by its incorporation of both the number of metastatic nodes and the total nodal yield. Two patients with the same number of positive nodes may have different prognostic profiles depending on the total number of nodes examined. Other nodal characteristics, including extranodal extension and the number of metastatic nodes, may also contribute to risk stratification in OCSCC [16]. The 5-year OS, DFS, and DSS in our cohort were 70.0%, 66.3%, and 80.7%, respectively. Comparisons with previously published cohorts should be made cautiously because differences in tumor stage, treatment, follow-up duration, and survival definitions can substantially affect reported outcomes. Several limitations should be acknowledged. The retrospective, single-center design introduces the possibility of selection and information bias. Because all patients underwent END, the study cannot directly compare END with observation or other approaches to management of the clinically negative neck. The optimal LNR threshold remains uncertain, and the 19% cutoff requires validation in independent cohorts. Variation in surgical and pathological techniques may also influence LNY and LNR. Finally, the relatively limited follow-up may restrict assessment of long-term outcomes. Despite these limitations, this study provides data from a South Asian cohort of cN0/rN0 OCSCC. In our population, an LNY of ≥18 nodes were not significantly associated with OS, whereas LNR demonstrated a significant association with 5-year OS. These findings support further evaluation of LNR as a prognostic marker, particularly through multicenter studies using standardized pathological assessment and validated LNR thresholds

In this cohort of clinically and radiologically node-negative oral cavity squamous cell carcinoma undergoing elective neck dissection, lymph node yield was not significantly associated with overall survival when categorized using a threshold of 18 nodes. In contrast, lymph node ratio demonstrated a significant association with overall survival, with patients in the higher LNR group showing substantially lower 5-year overall survival than those in the lower LNR group. These findings suggest that LNR may provide additional prognostic information beyond lymph node yield by incorporating both the burden of nodal metastasis and the total number of lymph nodes examined. Further prospective and multicenter studies are warranted to validate the prognostic utility and optimal cutoff of LNR in clinically node-negative oral cavity squamous cell carcinoma.

1. Pentenero M, Gandolfo S, Carrozzo M. Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral squamous cell carcinoma: a review of the literature. Head Neck. 2005;27(12):1080-1091. doi:10.1002/hed.20275. 2. Zbären P, Nuyens M, Caversaccio M, Stauffer E. Elective neck dissection for carcinomas of the oral cavity: occult metastases, neck recurrences, and adjuvant treatment of pathologically positive necks. Am J Surg. 2006;191(6):756-760. doi:10.1016/j.amjsurg.2006.01.052. 3. Ebrahimi A, Gil Z, Amit M, et al; International Consortium for Outcome Research in Head and Neck Cancer. Primary tumor staging for oral cancer and a proposed modification incorporating depth of invasion: an international multicenter retrospective study. JAMA Otolaryngol Head Neck Surg. 2014;140(12):1138-1148. doi:10.1001/jamaoto.2014.1548. 4. D'Cruz AK, Vaish R, Kapre N, et al; Head and Neck Disease Management Group. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med. 2015;373(6):521-529. doi:10.1056/NEJMoa1506007. 5. Ren ZH, Xu JL, Li B, Fan TF, Ji T, Zhang CP. Elective versus therapeutic neck dissection in node-negative oral cancer: evidence from five randomized controlled trials. Oral Oncol. 2015;51(11):976-981. doi:10.1016/j.oraloncology.2015.08.009. 6. Ebrahimi A, Zhang WJ, Gao K, Clark JR. Nodal yield and survival in oral squamous cancer: defining the standard of care. Cancer. 2011;117(13):2917-2925. doi:10.1002/cncr.25834. 7. Arain AA, Rajput MSA, Ansari SA, et al. Occult nodal metastasis in oral cavity cancers. Cureus. 2020;12(11):e11640. doi:10.7759/cureus.11640. 8. Hasegawa Y, Tsukahara K, Yoshimoto S, et al; HNCMM Research Group. Neck dissections based on sentinel lymph node navigation versus elective neck dissections in early oral cancers: a randomized, multicenter, and noninferiority trial. J Clin Oncol. 2021;39(18):2025-2036. doi:10.1200/JCO.20.03637. 9. Dudkiewicz D, Tsur N, Yaniv D, et al. Re-evaluating lymph node yield, lymph node ratio, and the number of metastatic nodes as prognostic factors in oral cavity squamous cell carcinoma. Oral Oncol. 2025;166:107391. doi:10.1016/j.oraloncology.2025.107391. 10. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 2007;4(10):e296. doi:10.1371/journal.pmed.0040296. 11. Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, et al., editors. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017. 12. Yamagata K, Fukuzawa S, Uchida F, et al. Is the addition of extranodal extension and lymph node yield of pN0 to the lymph node ratio useful as a prognostic parameter for patients with oral squamous cell carcinoma? Br J Oral Maxillofac Surg. 2021;59(8):941-946. doi:10.1016/j.bjoms.2020.12.009. 13. Ebrahimi A, Clark JR, Zhang WJ, Elliott MS, Gao K, Milross CG, Shannon KF. Lymph node ratio as an independent prognostic factor in oral squamous cell carcinoma. Head Neck. 2011;33(9):1245-1251. doi:10.1002/hed.21600. 14. Spoerl S, Gerken M, Mamilos A, et al. Lymph node ratio as a predictor for outcome in oral squamous cell carcinoma: a multicenter population-based cohort study. Clin Oral Investig. 2021;25(4):1705-1713. doi:10.1007/s00784-020-03471-6. 15. Beltramini GA, Belloni LM, Fusco N, et al. Comparing prognostic utility between the 8th edition of TNM staging system and the lymph node ratio for oral squamous cell carcinoma. Head Neck. 2021;43(10):2876-2882. doi:10.1002/hed.26769. 16. Arun I, Maity N, Hameed S, et al. Lymph node characteristics and their prognostic significance in oral squamous cell carcinoma. Head Neck. 2021. PMID:33021340.